The efficacy of chemopreventive agents is tested against clinically-normal colon epithelial cells derived from mice predisposed to colon cancer. The primary cell cultures are expanded in culture and assayed for surrogate biomarkers prior to and following their spontaneous immortalization in the presence or absence of chemopreventive agents. The mutant mice used are as follows: MIN, MLH1, APC/MLH1, and SMAD4.